Pyruvate kinase activators: targeting red cell metabolism in thalassemia

Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):114-120. doi: 10.1182/hematology.2023000468.ABSTRACTThalassemia is an inherited red blood cell disorder whereby the qualitative and/or quantitative imbalance in α- to β-globin ratio results in hemolysis and ineffective erythropoiesis. Oxidative stress, from the precipitated excess globin and free iron, is a major factor that drives hemolysis and ineffective erythropoiesis. Pyruvate kinase activity and adenosine triphosphate availability are reduced due to the overwhelmed cellular antioxidant system from the excessive oxidative stress. Mitapivat, a pyruvate kinase activator in development as a treatment for thalassemia, was shown to increase hemoglobin and reduce hemolysis in a small phase 2 single-arm trial of patients with α- and β-thalassemia. The ongoing phase 3 studies with mitapivat and the phase 2 study with etavopivat will examine the role of pyruvate kinase activators as disease modifying agents in thalassemia.PMID:38066911 | PMC:PMC10727068 | DOI:10.1182/hematology.2023000468
Source: Hematology ASH Education Program - Category: Hematology Authors: Source Type: research